Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse

Ken-Ichirou Morohashi, Hisae Tsuboi-Asai, Sumie Matsushita, Masahiro Suda, Manabu Nakashima, Hironobu Sasano, Yoshiaki Hataba, Chun Li Li, Junichi Fukata, Junji Irie, Takeshi Watanabe, Hiroshi Nagura, En Li

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The spleen has two main functions. The first is to provide a proper microenvironment to lymphoid and myeloid cells, whereas the second involves clearance of abnormal erythrocytes. Ad4BP/SF-1, a product of the mammalian FTZ-F1 gene (mFTZ-F1), was originally identified as a steroidogenic, tissue- specific transcription factor. Immunohistochemical examination of the mammalian spleens confirmed the expression of Ad4BP/SF-1 in endothelial cells of the splenic venous sinuses and pulp vein. In mFtz-F1 gene-disrupted (KO) mice, several structural abnormalities were detected in the spleen, including underdevelopment and nonuniform distribution of erythrocytes. Examination of the spleen of KO fetuses showed failure of development of certain tubular structures during embryogenesis. These structures are normally assembled by Ad4BP/SF-1 immunoreactive cells, and most likely form the vascular system during later stages of development. Other structural abnormalities in the spleen of the KO mice included defects in the tissue distribution of type-IV collagen, laminin, c-kit, and vimentin. These morphologic defects in the vascular system were associated with a decrease in the proportion of hematopoietic cells, although differentiation of these cells was not affected significantly. A high number of abnormal red blood cells containing Howell- Jolly bodies were noted in the KO mice, indicating impaired clearance by the splenic vascular system. We also detected the presence of an mRNA-encoding cholesterol side-chain cleavage P450 in the spleen, resembling the findings in steroidogenic tissues such as the gonads and adrenal cortex. The mRNA transcript was not involved in splenic structural defects as it was detected in the spleens of both normal and KO mice, indicating that the regulatory mechanism of the P450 gene in the spleen is different from that in steroidogenic tissues. Our results indicate that a lack of the mFtz-F1 gene in mice is associated with structural and functional abnormalities of the splenic vascular system.

Original languageEnglish
Pages (from-to)1586-1594
Number of pages9
JournalBlood
Volume93
Issue number5
Publication statusPublished - Mar 1 1999

Fingerprint

Spleen
Genes
Tissue
Defects
Blood Vessels
Cells
Messenger RNA
Collagen Type IV
Endothelial cells
Laminin
Vimentin
Pulp
Erythrocyte Inclusions
Abnormal Erythrocytes
Blood
Transcription Factors
Erythrocytes
Cholesterol
Adrenal Cortex
Gonads

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Morohashi, K-I., Tsuboi-Asai, H., Matsushita, S., Suda, M., Nakashima, M., Sasano, H., ... Li, E. (1999). Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. Blood, 93(5), 1586-1594.

Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. / Morohashi, Ken-Ichirou; Tsuboi-Asai, Hisae; Matsushita, Sumie; Suda, Masahiro; Nakashima, Manabu; Sasano, Hironobu; Hataba, Yoshiaki; Li, Chun Li; Fukata, Junichi; Irie, Junji; Watanabe, Takeshi; Nagura, Hiroshi; Li, En.

In: Blood, Vol. 93, No. 5, 01.03.1999, p. 1586-1594.

Research output: Contribution to journalArticle

Morohashi, K-I, Tsuboi-Asai, H, Matsushita, S, Suda, M, Nakashima, M, Sasano, H, Hataba, Y, Li, CL, Fukata, J, Irie, J, Watanabe, T, Nagura, H & Li, E 1999, 'Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse', Blood, vol. 93, no. 5, pp. 1586-1594.
Morohashi K-I, Tsuboi-Asai H, Matsushita S, Suda M, Nakashima M, Sasano H et al. Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. Blood. 1999 Mar 1;93(5):1586-1594.
Morohashi, Ken-Ichirou ; Tsuboi-Asai, Hisae ; Matsushita, Sumie ; Suda, Masahiro ; Nakashima, Manabu ; Sasano, Hironobu ; Hataba, Yoshiaki ; Li, Chun Li ; Fukata, Junichi ; Irie, Junji ; Watanabe, Takeshi ; Nagura, Hiroshi ; Li, En. / Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. In: Blood. 1999 ; Vol. 93, No. 5. pp. 1586-1594.
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AU - Suda, Masahiro

AU - Nakashima, Manabu

AU - Sasano, Hironobu

AU - Hataba, Yoshiaki

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AU - Fukata, Junichi

AU - Irie, Junji

AU - Watanabe, Takeshi

AU - Nagura, Hiroshi

AU - Li, En

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N2 - The spleen has two main functions. The first is to provide a proper microenvironment to lymphoid and myeloid cells, whereas the second involves clearance of abnormal erythrocytes. Ad4BP/SF-1, a product of the mammalian FTZ-F1 gene (mFTZ-F1), was originally identified as a steroidogenic, tissue- specific transcription factor. Immunohistochemical examination of the mammalian spleens confirmed the expression of Ad4BP/SF-1 in endothelial cells of the splenic venous sinuses and pulp vein. In mFtz-F1 gene-disrupted (KO) mice, several structural abnormalities were detected in the spleen, including underdevelopment and nonuniform distribution of erythrocytes. Examination of the spleen of KO fetuses showed failure of development of certain tubular structures during embryogenesis. These structures are normally assembled by Ad4BP/SF-1 immunoreactive cells, and most likely form the vascular system during later stages of development. Other structural abnormalities in the spleen of the KO mice included defects in the tissue distribution of type-IV collagen, laminin, c-kit, and vimentin. These morphologic defects in the vascular system were associated with a decrease in the proportion of hematopoietic cells, although differentiation of these cells was not affected significantly. A high number of abnormal red blood cells containing Howell- Jolly bodies were noted in the KO mice, indicating impaired clearance by the splenic vascular system. We also detected the presence of an mRNA-encoding cholesterol side-chain cleavage P450 in the spleen, resembling the findings in steroidogenic tissues such as the gonads and adrenal cortex. The mRNA transcript was not involved in splenic structural defects as it was detected in the spleens of both normal and KO mice, indicating that the regulatory mechanism of the P450 gene in the spleen is different from that in steroidogenic tissues. Our results indicate that a lack of the mFtz-F1 gene in mice is associated with structural and functional abnormalities of the splenic vascular system.

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